Clinical Trials Register

Summary
EudraCT Number:	2012-003995-38
Sponsor's Protocol Code Number:	CQAW039A2214
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-27
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-003995-38

A.3

Full title of the trial

A double-blind, placebo-controlled, study examining the effect of orally administered QAW039 (450 mg QD) on FEV1 and ACQ in non-atopic, asthmatic patients with a baseline, pre-bronchodilator FEV1 of 40-80% predicted, inadequately controlled with low dose ICS therapy

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A double-blind, placebo-controlled, clinical study examining the effect of QAW039 capsules on lung function and Astma control in non-atopic, asthmatic patients with a baseline lung function of 40-80% predicted, inadequately controlled with low dose therapy with inhaled corticosteroids

A.4.1

Sponsor's protocol code number

CQAW039A2214

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41 61 3241111
B.5.5	Fax number	+41 61 3248001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	QAW039
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not established
D.3.9.1	CAS number	872365-14-5
D.3.9.2	Current sponsor code	QAW039
D.3.9.3	Other descriptive name	QAW039-NXA.001
D.3.9.4	EV Substance Code	SUB32073
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Flovent Diskus 250
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fluticasone
D.3.9.1	CAS number	80474-14-2
D.3.9.3	Other descriptive name	FLUTICASONE PROPIONATE
D.3.9.4	EV Substance Code	SUB02241MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate-to-severe, persistent asthma, inadequately controlled
with ICS therapy.

E.1.1.1

Medical condition in easily understood language

Asthma.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to assess the efficacy of QAW039 (450 mg qd) compared to placebo with respect to the change in trough FEV1 from baseline to 12 weeks of post-baseline treatment in non-atopic asthmatic patients who, at randomization, were inadequately controlled on low dose ICS (100 μg fluticasone BID) background therapy.

E.2.2

Secondary objectives of the trial

The key secondary objective is to demonstrate that QAW039 provides superior control of asthmatic symptoms to placebo in non-atopic asthmatic patients, as measured by the asthma control questionnaire (ACQ-6)

Secondary Objectives:

• To compare the efficacy of QAW039 as an add-on therapy to
background ICS (100 μg fluticasone BID) with an increased dose of ICS (250 μg fluticasone BID) in inadequately controlled atopic asthmatics
• To compare the efficacy of QAW039 as an add-on therapy to background ICS (100 μg fluticasone BID) between non-atopic and atopic asthmatic patients
• To assess safety and tolerability of QAW039 in the non-atopic asthmatic population as compared to placebo

For further secondary and exploratory objectives please see protocol section 2.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained before any assessment is performed
2. Males and females of any race who are aged ≥18 years
3. Patients with a diagnosis of persistent asthma (according to GINA2011) for a period of at least 6 months prior to screening
4. Patients with a pre-bronchodilator FEV1 value of 40% to 80% of individual predicted value at screening and prior to treatment. The FEV1 results should meet the ATS/ERS criteria for acceptability and repeatability (in case of screening failure due to ATS/ERS criteria, rescreening is allowed once)
5. Patients must be either non-atopic as defined by:
a. A history of perennial symptoms with no clear inhaled allergic trigger AND
b. A negative skin prick test (< 3mm diameter above background) either historically or at Screening AND
c. A negative specific IgE (e.g. RAST/CAP) test (<0.35 IU eq./ml)either historically or against a defined panel of common aeroallergens
OR
atopic/allergic as diagnosed historically or at Screening by either a skin prick test (≥ 3mm diameter above background) or a positive specific IgE (e.g. RAST/CAP) test (≥0.35 IU eq./ml)
6. Patients who are demonstrated to have reversible airway obstruction or airways hyper-reactivity or have shown either of such responses in previous test(s) within the last year
• Reversible airway obstruction demonstrated at Screening is defined as either:
a. an increase of ≥12% and ≥200 ml in FEV1 over the patient’s pre-bronchodilator value in liters or
b. an increase of ≥10% in % of predicted FEV1 over the patient’s pre-bronchodilator % of predicted FEV1 within 10-15 minutes after inhaling a total of 360 μg of albuterol or 400 μg salbutamol via MDI (reversibility test). The administration of albuterol or salbutamol for the reversibility test is to be within 30 minutes after pre-bronchodilator spirometry.
A positive airways hyper-reactivity (AHR) test result is defined as a provoked fall in FEV1 of 20% (PC20) by methacholine at ≤8 mg/ml when not on ICS or ≤16 mg/ml on ICS therapy. The use of either histamine < 10mg/ml or acetylcholine < 20mg/ml in place of methacholine is also acceptable.
7. An ACQ7 score ≥ 1.5 prior to treatment.

E.4

Principal exclusion criteria

1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (CRTH2 antagonists)
3. History of long QT syndrome or whose current QTc measured at runin (Fridericia’s) is prolonged > 450 msec for males and females and confirmed by a central assessor
4. Pregnant or nursing (lactating) women
5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
6. Acute illness other than asthma at the start of the study
7. History of life-threatening asthma, including a history of significant hypercarbia (pCO2>45mmHg), prior intubation, respiratory arrest, or seizures as a result of asthma
8. Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening
9. Patients who have a clinically significant abnormality on a 12 lead ECG recorded within one month prior to screening. Patients who have a clinically significant abnormality on a 12-lead ECG recorded at run-in
10. Patients with serious co-morbidities including, but not limited to, uncontrolled diabetes (HbA1c ≥8%), heart failure, cancer, neurodegenerative diseases, rheumatoid arthritis and other autoimmune diseases

E.5 End points

E.5.1

Primary end point(s)

The primary objective of the study is to evaluate superiority of QAW039 over placebo (with low-dose ICS as the background therapy) for the non-atopic group. The primary efficacy variable is the change from baseline in trough FEV1 (24-hour post morning dose) measured. Trough is defined as the FEV1 measurement at 23 hr. 10 min post dose on the preceding day. The baseline FEV1 is defined as the FEV1 assessments taken in the clinic at Visit 202.

E.5.1.1

Timepoint(s) of evaluation of this end point

Visits 101, 102, 199

E.5.2

Secondary end point(s)

The secondary variables include the change from baseline in ACQ-6. The baseline is defined as the assessment measured at Visit 202 (Day 14), i.e. the first day of treatment period.

For more details / other assessments please see protocol section 6.

E.5.2.1

Timepoint(s) of evaluation of this end point

visits 101, 102, 201

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Colombia

Czech Republic

Germany

India

Korea, Republic of

Poland

Romania

South Africa

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

420

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

110

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

194

F.4.2.2

In the whole clinical trial

530

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients completing the treatment period will not be given further access to study drug because the risk/benefit ratio will not yet have been substantiated and there are already othermarketed therapeutic alternatives available to treat these patients. At the time of study completion or early termination, all patients will be placed on the appropriate asthma treatment as prescribed by the investigator.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-02-04

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